Dynamics of Nucleic Acids and Proteins Investigations of some contemporary issues

Abstract

Biomolecules are the building blocks of life that regulate the biological processes newlinewithin the organisms. The interplay of just three classes of biomolecules: DNA, newlineRNA and proteins provide complexity to the biological world. Their structures, newlinestabilities and dynamics are keys to understand the working of Nature. Advanced newlinebiophysical and biochemical techniques have proven useful to study the structure, newlinedynamics and local flexibilities within the biomolecules. However, most of these newlinesophisticated experimental techniques are complex and time consuming, apart from newlinebeing expensive. Also, they do not always directly provide an atomistic picture of newlinemacromolecular dynamics in situ with sufficient time resolution. In current scenario of enhanced computing power, computer simulations have emerged as a useful tool to not only better interpret experimental results; in several ways they complement experimental investigations. We have used simulation methods to probe newlinesome contemporary issues related to structural stability and functional dynamics newlineof biomolecules, with focus on nucleic acids and proteins. This thesis describes newlineinvestigations using simulation techniques as applied to three different systems, in newlineorder to address three types of issues related to biomolecular dynamics: functional newlinebehavior of purine (adenine, guanine) and lysine riboswitches; folding of small mitochondrial subunit binding protein and modeling the structure and possible functional dynamics of a drug target enzyme. The studies address a wide range of contemporary issues related to the compatibility between simulation methods used and newlinescientific questions asked. Thus, wherever possible, the work involves benchmarking of simulation conditions and analysis methods and attempts at reconciliation of newlineavailable experimental data with the interpretation of trajectory analysis results newline